BackgroundDiffusion‐weighted imaging (DWI) is an MRI technique with the potential to serve as an unenhanced breast cancer detection tool. Synthetic b‐values produce images with high diffusion weighting to suppress residual background signal, while avoiding additional measurement times and reducing artifacts.PurposeTo compare acquired DWI images (at b = 850 s/mm2) and different synthetic b‐values (at b = 1000–2000 s/mm2) in terms of lesion visibility, image quality, and tumor‐to‐tissue contrast in patients with malignant breast tumors.Study TypeRetrospective.PopulationFifty‐three females with malignant breast lesions.Field Strength/SequenceT2w, DWI EPI with STIR fat‐suppression, and dynamic contrast‐enhanced T1w at 3T.AssessmentFrom acquired images using b‐values of 50 and 850 s/mm2, synthetic images were calculated at b = 1000, 1200, 1400, 1600, 1800, and 2000 s/mm2. Four readers independently rated image quality, lesion visibility, preferred b‐value, as well as the lowest and highest b‐value, over the range of b‐values tested, to provide a diagnostic image.Statistical TestsMedians and mean ranks were calculated and compared using the Friedman test and Wilcoxon signed‐rank test. Reproducibility was analyzed by intraclass correlation (ICC), Fleiss, and Cohen's κ.ResultsRelative signal‐to‐noise and contrast‐to‐noise ratios decreased with increasing b‐values, while the signal‐intensity ratio between tumor and tissue increased significantly (P < 0.001). Intermediate b‐values (1200–1800 s/mm2) were rated best concerning image quality and lesion visibility; the preferred b‐value mostly lay at 1200–1600 s/mm2. Lowest and highest acceptable b‐values were 850 s/mm2 and 2000 s/mm2. Interreader agreement was moderate to high concerning image quality (ICC: 0.50–0.67) and lesion visibility (0.70–0.93), but poor concerning preferred and acceptable b‐values (κ = 0.032–0.446).Data ConclusionSynthetically increased b‐values may be a way to improve tumor‐to‐tissue contrast, lesion visibility, and image quality of breast DWI, while avoiding the disadvantages of performing DWI at very high b‐values.Level of Evidence: 3Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:1754–1761.